Today's Veterinary Practice

NOV-DEC 2018

Today's Veterinary Practice provides comprehensive information to keep every small animal practitioner up to date on companion animal medicine and surgery as well as practice building and management.

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PEER REVIEWED 28 NOVEMBER/DECEMBER 2018 perhaps not as clear how diseases like osteoarthritis can lead to neuropathic pain; this lack of clarity has contributed to the undertreatment of this condition. Although osteoarthritis and other chronic pain conditions may not involve direct nerve damage, chronic pain (especially if untreated or undertreated) can lead to pain pathway changes that are inherent to neuropathic pain, including ectopic activity in afferent nerves, peripheral sensitization, central sensitization, impaired inhibitory modulation, and pathologic activation of cells that are normally not active in the pain process. 6 Adding to the potential for undertreatment of chronic pain is the fact that these changes make chronic pain difficult to treat. The pain often no longer results from the inciting cause but rather results from these changes in the pain pathway. 3 Treatment of Chronic Pain Unfortunately, the changes that lead to chronic pain are neither predictable nor consistent, making pain a truly individual sensation that often requires individual therapy. However, we have a variety of drugs that may effectively treat chronic pain in general and some that treat neuropathic pain in particular. 3,5,6,7 This article focuses on 2 attainable and affordable options, gabapentin and amantadine, which are not only fairly specific for neuropathic pain, but are also nonopioid drugs. The opioid shortage has not threatened the supply of these drugs and diversion for human abuse is probably nonexistent. Neither drug is controlled by the Drug Enforcement Administration (DEA). Gabapentin and amantadine each has a greater potential than tramadol for effectively treating chronic pain because of their mechanisms of action. Tramadol, a class IV DEA-controlled drug, is commonly used in veterinary medicine yet is unlikely to be effective when used alone for treatment of either acute or chronic pain; it was recently shown to be ineffective for treatment of osteoarthritis pain in dogs. 8 This finding is not surprising because the opioid effects of tramadol in dogs are minimal. 9 However, tramadol may provide some mild analgesia that would be useful in a multimodal protocol because of tramadol's role as a serotonin and norepinephrine reuptake inhibitor, which may provide analgesia through modulation of the descending inhibitory limb of the pain pathway. Tramadol effectively treats osteoarthritis pain in cats, 10 but those who have tried administering this drug to cats know that it can be difficult because its taste seems to be especially noxious to cats. GABAPENTIN What Is Gabapentin? Gabapentin is a drug in the anticonvulsant class that is approved by the Food and Drug Administration (FDA) for treatment of seizures and certain neuropathic pain conditions in humans. It is commonly used off-label to treat seizures (not described in this article) and neuropathic pain in animals. The drug is structurally similar to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), which explains its name but not its mechanism of action. Although not completely defined, the primary mechanism of action is presynaptic inhibition of calcium channels (specifically the alpha-2-delta-1 subunit) and subsequent calcium influx, which leads to decreased release of excitatory neurotransmitters ( FIGURE 2 ). This is the mechanism for both seizure control and pain relief. Why Use Gabapentin? Gabapentin is useful because chronic pain commonly has a neuropathic component that FIGURE 2. Sites of action of gabapentin and amantadine at the neuronal synaptic cleft. During depolarization, calcium enters the presynaptic membrane to cause the release of excitatory transmitters. Gabapentin (G) blocks the influx of calcium; thus, no neurotransmitters are released. Amantadine (A) antagonizes the N-methyl-D-aspartate (NMDA) receptor on the postsynaptic side of the cleft, thereby blocking transmission of pain signals from those receptors. Both of these actions decrease the number of pain impulses that are transmitted from the spinal cord to the brain. G A

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